Project Summary/Abstract Non-alcoholic fatty liver disease (NAFLD) is an important risk factor of type 2 diabetes and cardiovascular disease (CVD). This proposed project will study the association between dietary patterns and NAFLD in participants of the Framingham Heart Study (FHS), a large population-based cohort study (Aim 1). In addition, this project will examine the whole blood-derived DNA methylation signatures associated with dietary patterns and NAFLD in FHS participants (Aim 2). Diet related DNA methylation signatures in the liver will be examined using samples collected from an existing randomized, controlled experimental trial in Ossabaw pigs (Aim 3). Completion of the proposed project will provide evidence for dietary recommendations designed specifically to prevent NAFLD. Second, it will identify epigenetic biomarkers of NAFLD and its severity. Third, information generated from this project will contribute to a better understanding of the molecular pathways linking diet and NAFLD, and will serve as a basis for future prevention and treatment strategies. The candidate, Dr. Jiantao Ma, is currently a postdoctoral fellow at NHLBI?s Population Sciences Branch, headed by Dr. Daniel Levy. Dr. Levy is also the Director of the FHS and will serve as the primary mentor in Dr. Ma?s Advisory Committee. The Branch has a longstanding, impressive record of conducting large epidemiologic studies of CVD and other disease outcomes, and an outstanding track record of successfully training young investigators. The Advisory Committee also includes two internationally recognized experts in nutrition and epidemiology, Dr. Frank B. Hu, Professor of Nutrition and Epidemiology at Harvard T.H. Chan School of Public Health (HSPH) and Professor of Medicine at Harvard Medical School, and Dr. Alice H. Lichtenstein, Senior Scientist and Director of the Cardiovascular Nutrition Laboratory at Jean Mayer USDA Human Nutrition Research Center on Aging and Stanley N. Gershoff Professor of Nutrition Science and Policy of the Friedman School of Nutrition Science and Policy at Tufts University. Through this K22 Career Transition Award proposal, Dr. Ma seeks to systematically acquire additional mentored research and career development training at NHLBI. With the support from his Advisory Committee members, the K22 award will establish a training framework to initiate the research program in preparation for his independent career. As detailed in the Career Development Plan, new scientific skills that will be acquired include general training in genomics, techniques regarding data collection and management, and advanced statistical methods for complex omics data analysis through a combination of specialized coursework and hands-on training. The scientific training will support Dr. Ma to complete the proposed studies outlined in the Research Strategy. This will serve as the foundation for Dr. Ma?s future R01 grant and additional independent funding application upon his transition to independence. Dr. Ma will also participate in extensive career development training during the intramural mentored phase. Dr. Ma will be trained in mentoring, teaching, management, and leadership through courses, seminars, and workshops specifically developed for emerging junior investigators. In this phase of career development training, Dr. Ma will receive counselling on career paths in biomedical research, guidance on grant writing, and training on effective communication of scientific results to both the research and non-research communities. Dr. Ma?s Advisory Committee will evaluate his progress on the proposed research and career development training. This training opportunity will allow Dr. Ma to master knowledge and skills needed to become a well-rounded, multidisciplinary biomedical researcher in the extramural phase of this award and beyond. Dr. Ma?s long-term goal is to establish himself as an accomplished scientist and professor in a prestigious academic research institute, where he can study the pathogenesis of CVD and related chronic disease and to leverage results obtained in observational studies to implement in intervention studies for prevention and treatment of CVD. In summary, in this proposal for the NHLBI K22 Award, Dr. Ma will systematically examine dietary factors, biomarkers, and metabolic pathways related to NAFLD. With support from his Advisory Committee members and the K22 award, Dr. Ma will acquire additional scientific training, particularly in molecular epidemiology (DNA methylation and gene expression), and rich career development training. This training opportunity will facilitate Dr. Ma?s successful transition to become an independent investigator in the area of cardiovascular epidemiology.